Study Unlocks Brain Mystery of Ritalin

      NEW YORK, Jan 19 (Reuters Health) - Doctors have been prescribing Ritalin for years to treat attention-deficit/hyperactivity disorder (ADHD) in children, but exactly how the stimulant helps young people calm down and pay attention has been unclear.

      Now, researchers at the Brookhaven National Laboratory in Upton and the State University of New York at Stony Brook report that the medication appears to work by increasing levels of the brain chemical dopamine.   And they think they also know why the drug--unlike other dopamine-triggering medications--is not addictive when given to children.

      Dopamine, a hormone that plays a role in feelings of pleasure, is also intimately involved with the motivational process, according to the study's lead author, Dr. Nora D. Volkow.  By increasing dopamine levels in the brain, the drug may increase interest in activities that normally do not hold the attention of a child with ADHD, she told Reuters Health in an interview.

      For instance, after taking Ritalin, an arithmetic problem might become more interesting to a child who is normally turned off by math, Volkow noted.

"All of a sudden, it's not boring," she said.

      Previous research in animals and people had shown that Ritalin, also known by its generic name methylphenidate, increases dopamine levels, but the studies involved injections of doses much higher than normally prescribed to children.

      To see whether the smaller oral doses of Ritalin that are usually prescribed to children have the same effects, Volkow's team conducted a study involving 11 healthy men who did not have a history of drug or alcohol abuse and who were not taking any medications.

      The men's brains were scanned using technology called positron emission tomography.   One scanning session occurred after the men had taken Ritalin, while the other took place after they had taken a placebo, which did not contain any medication.

      About an hour after the men took Ritalin, dopamine levels in their brains increased significantly, Volkow's team reports in the January 15th issue of The Journal of Neuroscience.   The drug appears to raise levels of the hormone by blocking the activity of dopamine transporters, which remove dopamine once it has been released.

      According to Volkow, two groups of researchers have previously shown that some people with ADHD have too many of these dopamine transporters.  What this means, she said, is that the transporters "clean up" dopamine in the brain too quickly, making it difficult for the brain to pay attention.   By blocking these transporters, Ritalin appears to keep dopamine levels high enough so that a child does not lose interest, she explained.

      The findings may also help explain why Ritalin, when used as recommended, is not addictive, according to the New York researcher.

      Ritalin does increase dopamine levels, as do many addictive drugs including cocaine, alcohol and amphetamines, but the key difference may be the length of time the drugs take to reach the brain, Volkow said.  She noted that a drug must reach the brain very quickly for it to become addictive. On average, it takes an oral dose of Ritalin about an hour to have an effect on the brain, she said, which prevents the drug from causing the "high" produced by most drugs that stimulate dopamine.

      This lag explains why children who take appropriate doses of Ritalin (based on a child's weight, age and metabolism) do not become addicted to the stimulant, Volkow said.   However, she pointed out that Ritalin can become addictive when tablets are crushed and then either snorted or injected, which makes the drug reach the brain much more rapidly.